Curtin was a strong supporter of President Lincoln's policies in the Civil War, and Curtin committed Pennsylvania to the war effort.[5] Curtin organized the Pennsylvania Reserves into combat units, and oversaw the construction of the first Union military camp for training militia. It opened in an agricultural school nearby Harrisburg as Camp Curtin on April 18, 1861, and more than 300,000 men were drilled there during 4 years. In the years that followed, Curtin became a close friend and confidant of Abraham Lincoln, visiting the White House several times in order to converse about the status of the war effort.

After the Battle of Gettysburg, Governor Curtin was the principal force behind the establishment of the National Cemetery there. Through his agent, David Wills, Curtin procured the attendance of President Abraham Lincoln at the dedication of the cemetery. Governor Curtin was sitting with Lincoln on the platform on November 19, 1863, when Lincoln delivered his Gettysburg Address.

In his first term, Governor Curtin suffered a severe breakdown from the stresses of war. Secretary of State Eli Slifer handled governmental affairs during the increasingly frequent periods when Curtin was incapacitated. President Lincoln offered the governor a diplomatic position abroad, but he chose to run for reelection in 1863.

To coordinate Union war efforts, Curtin convened the Loyal War Governors' Conference on September 24 and 25, 1862, in Altoona. This event was one of his most significant contributions to the Union war effort. He formed the Pennsylvania State Agency in Washington, and another branch in Nashville, Tennessee, to provide support for wounded soldiers on the battlefield and returned home. He also founded the state-funded Orphan's School to aid and educate children of military men who had died for the Union cause.

Curtin's family was prominent in Pennsylvania politics and in the Civil War. He was the great-grandson of James Potter, the vice-president of Pennsylvania, and was the grandson of Andrew Gregg, also a prominent Pennsylvania politician. He was the uncle of John I. Gregg and cousin of David McMurtrie Gregg, both Union generals in the Civil War. He was also a cousin of Col. John I. Curtin.